ArticleNature genetics2012
Inhibition of RNA lariat debranching enzyme suppresses TDP-43 toxicity in ALS disease models.
Article in Nature genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
169 citing papers in PubMed, 2 syntheses or guidelines pooled it, 255 citations in OpenAlex.
- A systematic review of the research progress of non-coding RNA in neuroinflammation and immune regulation in cerebral infarction/ischemia-reperfusion injury.Frontiers in immunology · 2022Pooled it
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- Intron retention in health and amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Review
- RNA-Binding Protein TAF15 Suppresses Toxicity in a Yeast Model of FUS Proteinopathy.Journal of fungi (Basel, Switzerland) · 2026Article
- Predictive Cellular Signatures from Live Human Motor Neurons Distinguish TDP-43 ALS and Enable ALS Subtype Stratification.bioRxiv : the preprint server for biology · 2026Article
- Article
- Reduction of RAD23A extends lifespan and mitigates pathology in a mouse model of TDP-43 proteinopathy.Nature communications · 2026Article
- Scp160 deletion suppresses TDP-43 aggregation and toxicity inMicrobial cell (Graz, Austria) · 2026Article
- Solid Phase Chemical Synthesis of RNA.Methods in molecular biology (Clifton, N.J.) · 2026Article
- From Yeast to Therapeutics: Modeling Neurodegenerative Diseases in Saccharomyces cerevisiae.Yeast (Chichester, England) · 2025Review
- Multiplex neurodegeneration proteotoxicity platform reveals DNAJB6 promotes non-toxic FUS condensate gelation and inhibits neurotoxicity.Nature communications · 2025Article
- A single-cell, long-read, isoform-resolved case-control study of FTD reveals cell-type-specific and broad splicing dysregulation in human brain.Cell reports · 2025Article
- DEAD-Box Helicase 3 Modulates the Non-Coding RNA Pool in Ribonucleoprotein Condensates During Stress Granule Formation.Non-coding RNA · 2025Article
- DBR1 orchestrates the fate of lariat RNA: debranching-dependent turnover and function.Nucleic acids research · 2025Review
- Circular RNA expression in ALS is progressively deregulated and tissue-dependent.BMC genomics · 2025Article
- AAV-based delivery of RNAi targeting ataxin-2 improves survival and pathology in TDP-43 mice.Nature communications · 2025Article
- iHofman: a predictive model integrating high-order and low-order features with weighted attention mechanisms for circRNA-miRNA interactions.BMC biology · 2025Article
- Scouring the human Hsp70 network uncovers diverse chaperone safeguards buffering TDP-43 toxicity.bioRxiv : the preprint server for biology · 2025Article
- Context-dependent Interactors Regulate TDP-43 Dysfunction in ALS/FTLD.bioRxiv : the preprint server for biology · 2025Article
- A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies inJournal of fungi (Basel, Switzerland) · 2025Review
109 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease primarily affecting motor neurons. Mutations in the gene encoding TDP-43 cause some forms of the disease, and cytoplasmic TDP-43 aggregates accumulate in degenerating neurons of most individuals with ALS. Thus, strategies aimed at targeting the toxicity of cytoplasmic TDP-43 aggregates may be effective. Here, we report results from two genome-wide loss-of-function TDP-43 toxicity suppressor screens in yeast. The strongest suppressor of TDP-43 toxicity was deletion of DBR1, which encodes an RNA lariat debranching enzyme. We show that, in the absence of Dbr1 enzymatic activity, intronic lariats accumulate in the cytoplasm and likely act as decoys to sequester TDP-43, preventing it from interfering with essential cellular RNAs and RNA-binding proteins. Knockdown of Dbr1 in a human neuronal cell line or in primary rat neurons is also sufficient to rescue TDP-43 toxicity. Our findings provide insight into TDP-43-mediated cytotoxicity and suggest that decreasing Dbr1 activity could be a potential therapeutic approach for ALS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.